Interactions of chromatin-remodelling complexes with RNA are known; however, their significance is poorly understood. Chen et al. studied the chromatin-activating complex Tip60–p400 (an acetyltransferase) and found that it was able to bind to nascent transcripts near their initiation start sites, and that this binding was enhanced by the presence of DNA:RNA hybrids (R loops) between the transcript and the DNA template. At the same time, binding of the Polycomb repressive complex 2 (PRC2) was found to be inhibited by the formation of R loops. Thus, the presence of R loops near the 5′ ends of transcribed genes affects the recruitment of chromatin remodellers to these sites, thereby shaping chromatin structure and influencing transcription. Moreover, the authors provided evidence that the disruption of R loops perturbed stem cell differentiation, indicating that the absence of R loops can lead to global changes in gene expression.